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  Fourthuniversaldefinitionofmyocardialinfarction(2018) Kristian Thygesen* (Denmark), Joseph S. Alpert* (USA), Allan S. Jaffe (USA),Bernard R. Chaitman (USA), Jeroen J. Bax (The Netherlands), David A. Morrow(USA), Harvey D. White* (New Zealand): the Executive Group on behalf of the JointEuropean Societyof Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial InfarctionAuthors/Task Force Members/Chairpersons: Kristian Thygesen* (Denmark), JosephS. Alpert* (USA), Allan S. Jaffe (USA), Bernard R. Chaitman (USA), Jeroen J. Bax(The Netherlands), David A. Morrow (USA), Harvey D. White* (New Zealand),Hans Mickley (Denmark), Filippo Crea (Italy), Frans Van de Werf (Belgium), ChiaraBucciarelli-Ducci (UK), Hugo A. Katus (Germany), Fausto J. Pinto (Portugal), ElliottM. Antman (USA), Christian W. Hamm (Germany), Raffaele De Caterina (Italy), James L. Januzzi Jr (USA), Fred S. Apple (USA), Maria Angeles Alonso Garcia(Spain), S. Richard Underwood (UK), John M. Canty Jr (USA), Alexander R. Lyon(UK), P. J. Devereaux (Canada), Jose Luis Zamorano (Spain), Bertil Lindahl(Sweden), William S. Weintraub (USA), L. Kristin Newby (USA), Renu Virmani(USA), Pascal Vranckx (Belgium), Don Cutlip (USA), Raymond J. Gibbons (USA),Sidney C. Smith (USA), Dan Atar (Norway), Russell V. Luepker (USA), Rose MarieRobertson (USA), Robert O. Bonow (USA), P. Gabriel Steg (France), Patrick T.O’Gara (USA), Keith A. A. Fox (UK) * Corresponding authors. Kristian Thygesen, Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard, DK-8200 Aarhus N, Denmark. Tel:  þ 4578452262, Fax: þ 45 78452260, Email: kthygesen@oncable.dk; kristhyg@rm.dk. Joseph S. Alpert, Department of Medicine, University of Arizona College of Medicine, 1501 N.Campbell Ave., P.O. Box 245037, Tucson AZ 85724-5037, USA. Tel: þ 1 5206262763, Email: jalpert@email.arizona.edu. Harvey D. White, Green Lane Cardiovascular Service,Auckland City Hospital, Private Bag 92024, 1030 Auckland, New Zealand. Tel: þ 64 96309992, Fax: 00 64 9 6309915, Email: harveyw@adhb.govt.nz.The content of this ESC/ACC/AHA/WHF Expert Consensus Document has been published for personal and educational use only. No commercial use is authorized. No part of  the ESC/ACC/AHA/WHF Expert Consensus Document may be translated or reproduced in any form without written permission from the ESC or ACC or AHA or WHF.Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handlesuch permissions on behalf of the ESC, ACC, AHA and WHF ( journals.permissions@oxfordjournals.org). Disclaimer  . The ESC/ACC/AHA/WHF Expert Consensus Document represents the views of the ESC, ACC, AHA, and WHF and was produced after careful consideration of  the scientific and medical knowledge and the evidence available at the time of their publication. The ESC, ACC, AHA, and WHF are not responsible in the event of any contra-diction, discrepancy, and/or ambiguity between the ESC/ACC/AHA/WHF Expert Consensus Document and any other official recommendations or Expert Consensus Documentissued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC/ACC/AHA/WHF Expert Consensus Document fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive,diagnostic, or therapeutic medical strategies; however, the ESC/ACC/AHA/WHF Expert Consensus Document does not override, in any way whatsoever, the individual responsi-bility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, whereappropriate and/or necessary, the patient’s caregiver. Nor does the ESC/ACC/AHA/WHF Expert Consensus Document exempt health professionals from taking into full andcareful consideration the relevant official updated recommendations or Expert Consensus Documents issued by the competent public health authorities, in order to manageeach patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility toverify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.This article has been co-published in  European Heart Journal, Journal of the American College of Cardiology, Circulation , and  Global Heart  . All rights reserved. V C 2018 European Society of Cardiology, American College of Cardiology, American Heart Association, Inc., and World Heart Foundation. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Any citation can be used when citing this article. European Heart Journal (2018)  00 , 1–33  EXPERT CONSENSUS DOCUMENT doi:10.1093/eurheartj/ehy462 D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   a d v  an c  e- ar  t  i   c l   e- a b  s  t  r  a c  t   /   d  oi   /  1  0 .1  0  9  3  /   e ur h  e ar  t   j   /   eh  y 4  6 2  /   5  0 7  9  0  8 1  b  y  g u e s  t   on 0  5 D e c  em b  er 2  0 1  8   ......................................................................... Document Reviewers: David Hasdai (CPG Review Co-ordinator) (Israel), Victor Aboyans (France),Stephan Achenbach (Germany), Stefan Agewall (Norway), Thomas Alexander (India), Alvaro Avezum(Brazil), Emanuele Barbato (Italy), Jean-Pierre Bassand (France), Eric Bates (USA), John A. Bittl (USA),Gu¨enter Breithardt (Germany), He´ctor Bueno (Spain), Raffaele Bugiardini (Italy), Mauricio G. Cohen(USA), George Dangas (USA), James A. de Lemos (USA), Victoria Delgado (Netherlands), GerasimosFilippatos (Greece), Edward Fry (USA), Christopher B. Granger (USA), Sigrun Halvorsen (Norway), MarkA. Hlatky (USA), Borja Ibanez (Spain), Stefan James (Sweden), Adnan Kastrati (Germany), ChristopheLeclercq (France), Kenneth W. Mahaffey (USA), Laxmi Mehta (USA), Christian Mu¨ller (Switzerland),Carlo Patrono (Italy), Massimo Francesco Piepoli (Italy), Daniel Pi ~ neiro (Argentina), Marco Roffi(Switzerland), Andrea Rubboli (Italy), Samin Sharma (USA), Iain A. Simpson (UK), Michael Tendera (Poland), Marco Valgimigli (Switzerland), Allard C. van der Wal (Netherlands), Stephan Windecker(Switzerland)The disclosure forms of all experts involved in the development of this Expert Consensus Document areavailable on the ESC website www.escardio.org/guidelines ................................................................................................................................................................................................... Keywords  Expert Consensus Document  ã  Myocardial infarction  ã  Type 1 MI  ã  Type 2 MI  ã  Type 3 MI  ã  Type 4aMI  ã  Type 4b MI  ã  Type 4c MI  ã  Type 5 MI  ã  Cardiac troponin  ã  High sensitivity cardiac troponin  ã Myocardial injury  ã  Prior myocardial infarction  ã  Silent myocardial infarction  ã  Recurrent myocardialinfarction  ã  Re-infarction  ã  Cardiac procedural myocardial injury  ã  Takotsubo syndrome  ã  Myocardial infarc- tion with non-obstructive coronary arteries (MINOCA) Table of contents Abbreviationsandacronyms . ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. . 31 WhatisnewintheUniversalDefinitionofMyocardialInfarction? . ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. . 42 Universaldefinitionsofmyocardialinjuryandmyocardialinfarction:summary ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. . 53 Introduction .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. . 64 Pathological characteristicsofmyocardialischaemiaandinfarction .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. . 75 Biomarkerdetectionofmyocardial injury andinfarction .. ... .. ... .. . 76 Clinicalpresentationsofmyocardialinfarction .. .. ... .. ... ... .. ... .. . 97 Clinicalclassification ofmyocardial infarction ... .. ... .. ... ... .. ... .. . 97.1 Myocardialinfarctiontype1 .. .. ... .. ... ... .. ... .. ... ... .. ... .. . 97.2 Myocardialinfarctiontype2 .. .. ... .. ... ... .. ... .. ... ... .. ... . 107.3 Myocardialinfarctiontype2andmyocardial injury . ... ... .. ... . 127.4 MyocardialInfarctiontype 3 .. .. ... .. ... ... .. ... .. ... ... .. ... . 128 Coronaryprocedure-relatedmyocardial injury . .. ... .. ... ... .. ... . 139 Myocardialinfarctionassociatedwith percutaneouscoronaryintervention (type4amyocardialinfarction) ... ... .. ... .. ... ... .. ... . 1410Stent/scaffoldthrombosisassociatedwith percutaneouscoronaryintervention(type 4bmyocardialinfarction) . .. ... ... .. ... . 1511Restenosisassociatedwithpercutaneouscoronaryintervention(type 4cmyocardialinfarction) .. ... .. ... .. ... ... .. ... .. ... ... .. ... . 1512Myocardial infarctionassociatedwithcoronaryarterybypassgrafting(type5 myocardial infarction) .. ... ... .. ... .. ... ... .. ... .. ... 1513Otherdefinitionsofmyocardial infarctionrelatedtopercutaneouscoronaryinterventionorcoronary artery bypassgrafting .. .. ... .. ... 1614Recurrentmyocardial infarction .. .. ... ... .. ... .. ... ... .. ... .. ... 1615Re-infarction .. .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... 1616Myocardial injuryandinfarctionassociatedwithcardiacproceduresotherthanrevascularization .. ... .. ... .. ... ... .. ... .. ... 1617Myocardial injuryandinfarctionassociatedwithnon-cardiac procedures .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... 1618Myocardial injuryorinfarctionassociatedwithheartfailure .. .. ... 1719Takotsubosyndrome . ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... 1720Myocardial infarctionwithnon-obstructivecoronaryarteries .. ... 1721Myocardial injuryand/orinfarctionassociatedwithkidneydisease . ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... 1722Myocardial injuryand/orinfarctionin criticallyillpatients . ... .. ... 1723Biochemical approachfordiagnosingmyocardial injuryandinfarction .. ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... 1724Analyticalissuesofcardiactroponins .. ... .. ... .. ... ... .. ... .. ... 2025The99th percentileupperreferencelimit . .. ... .. ... ... .. ... .. ... 2026Operationalizingcriteriaformyocardialinjuryandinfarction . .. ... 2027Electrocardiographic detectionofmyocardial infarction .. ... .. ... 2128Applicationofsupplemental electrocardiogramleads ... .. ... .. ... 2229Electrocardiographic detectionofmyocardial injury . ... .. ... .. ... 23 2  Expert consensus document D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   a d v  an c  e- ar  t  i   c l   e- a b  s  t  r  a c  t   /   d  oi   /  1  0 .1  0  9  3  /   e ur h  e ar  t   j   /   eh  y 4  6 2  /   5  0 7  9  0  8 1  b  y  g u e s  t   on 0  5 D e c  em b  er 2  0 1  8   ...................................................................................................................................... 30Priororsilent/unrecognizedmyocardial infarction .. .. ... ... .. ... . 2331Conditionsthatconfoundtheelectrocardiographicdiagnosisofmyocardialinfarction . ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2332Conductiondisturbancesandpacemakers . ... .. ... .. ... ... .. ... . 2433Atrialfibrillation ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2434Imagingtechniques. .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2434.1Echocardiography .. .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2434.2Radionuclideimaging . ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2234.3Cardiacmagneticresonance imaging .. ... .. ... .. ... ... .. ... . 2234.4Computedtomographiccoronary angiography .. ... ... .. ... . 2635Applyingimagingin acutemyocardialinfarction . ... .. ... ... .. ... . 2636Applyingimagingin latepresentationofmyocardial infarction . ... . 2637Regulatoryperspective onmyocardial infarctioninclinicaltrials .. .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2638Silent/unrecognizedmyocardial infarctioninepidemiologicalstudiesandquality programmes . ... .. ... .. ... ... .. ... .. ... ... .. ... . 2739Individual andpublic implicationsofthemyocardialinfarction definition ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2740Globalperspectivesofthedefinitionofmyocardial infarction . ... . 2741UsingtheUniversal Definition ofMyocardial Infarction in thehealthcaresystem . ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2742Appendix . .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2843Acknowledgements.. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 2844References .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... . 28 Abbreviations and acronyms ACC American College of CardiologyACS Acute coronary syndromeAHA American Heart AssociationARC-2 Academic Research Consortium-2AUC Area under the curveCAD Coronary artery diseaseCABG Coronary artery bypass graftingCKD Chronic kidney diseaseCK-MB Creatine kinase MB isoformCMR Cardiac magnetic resonanceCTCA Computed tomographic coronary angiographycTn Cardiac troponincTnI Cardiac troponin IcTnT Cardiac troponin TCT Computed tomographyCV Coefficient of variationEF Ejection fractionECG Electrocardiogram or electrocardiographicHF Heart failurehs-cTn High-sensitivity cardiac troponinIFCC International Federation of Clinical Chemistry andLaboratory MedicineISFC International Society and Federation of CardiologyLAD Left anterior descending arteryLBBB Left bundle branch block;LoD Limit of detectionLGE Late gadolinium enhancementLGE-CMR Late gadolinium enhancement cardiac magneticresonanceLV Left ventricular LVH Left ventricular hypertrophyMI Myocardial infarctionMINOCA Myocardial infarction with non-obstructive coronaryarteriesMONICA MONItoring of trends and determinants inCArdiovascular diseaseMPS Myocardial perfusion scintigraphyNHLBI National Heart, Lung, and Blood InstituteNSTEMI Non-ST-elevation myocardial infarctionPET Positron emission tomographyPCI Percutaneous coronary interventionPOC Point of careRBBB Right bundle branch block SPECT Single photon emission computed tomographySTEMI ST-elevation myocardial infarctionST-T ST-segment  –  T waveTIMI Thrombolysis in Myocardial InfarctionTTS Takotsubo syndromeUDMI Universal Definition of Myocardial InfarctionURL Upper reference limit WHF World Heart Federation WHO World Health Organization Expert consensus document  3 D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   a d v  an c  e- ar  t  i   c l   e- a b  s  t  r  a c  t   /   d  oi   /  1  0 .1  0  9  3  /   e ur h  e ar  t   j   /   eh  y 4  6 2  /   5  0 7  9  0  8 1  b  y  g u e s  t   on 0  5 D e c  em b  er 2  0 1  8   1 What is new in the Universal Definition of Myocardial Infarction? What’s new in the universal definition of myocardial infarction? New concepts ã Differentiation of myocardial infarction from myocardial injury.ã Highlighting peri-procedural myocardial injury after cardiac and non-cardiac procedures as discrete from myocardial infarction.ã Consideration of electrical remodelling (cardiac memory) in assessing repolarization abnormalities with tachyarrhythmia, pacing, and rate-related conduction disturbances.ã Use of cardiovascular magnetic resonance to define aetiology of myocardial injury.ã Use of computed tomographic coronary angiography in suspected myocardial infarction. Updated concepts ã Type 1 myocardial infarction: Emphasis on the causal relationship of plaque disruption with coronary athero-thrombosis; new Figure 3 .ã Type 2 myocardial infarction: Settings with oxygen demand and supply imbalance unrelated to acute coronary athero-thrombosis; new Figures 4 and 5 .ã Type 2 myocardial infarction: Relevance of presence or absence of coronary artery disease to prognosis and therapy.ã Differentiation of myocardial injury from type 2 myocardial infarction; new Figure 6 .ã Type 3 myocardial infarction: Clarify why type 3 myocardial infarction is a useful category to differentiate from sudden cardiac death.ã Types 4–5 myocardial infarction: Emphasis on distinction between procedure-related myocardial injury and procedure-related myocardial infarction.ã Cardiac troponin: Analytical issues for cardiac troponins; new Figure 7  .ã Emphasis on the benefits of high-sensitivity cardiac troponin assays.ã Considerations relevant to the use of rapid rule-out and rule-in protocols for myocardial injury and myocardial infarction.ã Issues related to specific diagnostic change ('delta') criteria for the use of cardiac troponins to detect or exclude acute myocardial injury.ã Consideration of new non-rate-related right bundle branch block with specific repolarization patterns.ã ST-segment elevation in lead aVR with specific repolarization patterns, as a STEMI equivalent.ã ECG detection of myocardial ischaemia in patients with an implantable cardiac defibrillator or a pacemaker.ã Enhanced role of imaging including cardiac magnetic resonance imaging for the diagnosis of myocardial infarction; new Figure 8 . New sections ã Takotsubo syndrome.ã MINOCA. ã Chronic kidney disease.ã Atrial fibrillation.ã Regulatory perspective on myocardial infarction.ã Silent or unrecognized myocardial infarction.    ©   E   S   C    /   A   C   C    /   A   H   A    /   W   H   F   2   0   1   8 ECG = electrocardiogram; MINOCA = myocardial infarction with non-obstructive coronary arteries; STEMI = ST-elevation myocardial infarction. 4  Expert consensus document D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   a d v  an c  e- ar  t  i   c l   e- a b  s  t  r  a c  t   /   d  oi   /  1  0 .1  0  9  3  /   e ur h  e ar  t   j   /   eh  y 4  6 2  /   5  0 7  9  0  8 1  b  y  g u e s  t   on 0  5 D e c  em b  er 2  0 1  8 
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